Breast cancer cells form primary tumors on ex vivo four-dimensional lung model.

BACKGROUND: Breast cancer mortality is most common in cancer in women, and there are no ex vivo models that can capture the primary growth of tumor with fidelity to the in vivo tumor growth. In this study, we grew human breast cancer cell lines in an acellular lung matrix of the ex vivo four-dimensional lung model to determine if they form primary tumor and the extent to which they mimic the histology and characteristics of the human tumors. MATERIALS AND METHODS: Rat lungs were harvested, decellularized, and placed in a bioreactor. To study the primary tumor growth, we seeded the lung via the trachea with human breast cancer cells SUM159, MCF7, or MDMB231 and perfused the pulmonary artery with oxygenated media. Lobectomies were performed and processed for hematoxylin and eosin, Ki-67, caspase-3, estrogen receptor, and progesterone receptor antibodies. RESULTS: All three cell lines grew in the ex vivo four-dimensional model and formed perfusable tumor nodules with similar histology and morphology as the primary tumors. SUM159 and MDAMB231 showed higher proliferation and apoptotic indices than MCF7. In addition, MCF7 retained its estrogen receptor and progesterone receptor positivity, whereas SUM159 and MDAMB 231 did not have any staining. CONCLUSIONS: Overall, our study showed that human breast cancer cells can be grown on the ex vivo four-dimensional lung model, which then form primary tumor nodules that mimic the morphology and histology of the original tumor.

Circulating tumor cells from 4D model have less integrin beta 4 expression.

BACKGROUND: Currently, there is no in vitro or ex vivo model that can isolate circulating tumor cells (CTCs). Recently, we developed a four-dimensional (4D) lung cancer model that allows for the isolation of CTCs. We postulated that these cells have different properties than parental (2D) cells. MATERIALS AND METHODS: We obtained CTCs by growing A549, H1299, 393P, and 344SQ cell lines on the 4D lung model. The CTCs were functionally characterized in vitro and gene expression of the cell adhesion molecules was compared with respective 2D cells. Integrin beta 4 (ITGB4) was further investigated by stably transfecting the A549 and H1299 cells. RESULTS: We found that all cell lines produced CTCs, and that CTCs from the 4D model were less adherent to the plastic and have a slower growth rate than respective 2D cells (P < 0.01). Most of the cell adhesion molecules were downregulated (P < 0.05) in CTCs, and ITGB4 was the common molecule, significantly more underexpressed in CTCs from all cell lines than their respective 2D cells. The modulation of ITGB4 led to a differential function of 2D cells. CONCLUSIONS: CTCs from the 4D model have different transcriptional, translational, and in vitro characteristics than the same cells grown on a petri dish, and these CTCs from the 4D model have the properties of CTCs that are responsible for metastasis.

A retrospective analysis of molecular testing in cytologically indeterminate thyroid nodules with histologic correlation: Experience at a heterogenous multihospital system.

INTRODUCTION: Thyroid malignancy is one of the most common types of cancer in developed nations. Currently, fine-needle aspiration cytology (FNAC) is the most practical screening test for thyroid nodules. However, cytologically indeterminate samples comprise approximately 15%-30% of cases. These include cases classified as atypia of undetermined significance (AUS), follicular neoplasm (FN), and suspicious for malignancy (SFM). Indeterminate cases can be sent for molecular testing for more definitive classification to help guide management and prevent overtreatment of benign thyroid nodules. We conducted a retrospective review on molecular testing of indeterminate thyroid FNAC and reviewed subsequent histologic diagnoses in resection specimens to assess how molecular testing supported a diagnosis and its effect on clinical management of patients at our institution. METHODS: A retrospective chart review was performed on all thyroid FNAC specimens, corresponding molecular testing, and subsequent surgical resection specimens over a 6-year period. RESULTS: A total of 10,253 thyroid FNAC were performed in our hospital system during our study period, of which 10% (n = 1102/10,253) had indeterminate FNAC results. Molecular testing was performed in 16% (n = 178/1102) of indeterminate cytology cases. Genetic alterations were identified in 39% (n = 69/178) of the cases sent for molecular testing. The majority of cytologically indeterminate cases sent for molecular testing were follicular-patterned lesions and their corresponding resection specimens revealed mostly low grade follicular derived neoplasms (i.e., follicular adenoma, non-invasive follicular thyroid neoplasm with papillary-like nuclear features, and follicular variant of papillary thyroid carcinoma). Of the cases with identified genetic alterations, 75% (n = 52/69) were treated surgically. In cases with no genetic alterations identified, only 18% (n = 20/109) were treated surgically. DISCUSSION/CONCLUSION: Molecular testing on cytologically indeterminate thyroid nodules can help provide a more accurate risk of malignancy assessment in patients with lesions that are difficult to diagnosis based solely on FNAC morphology. The types of genetic alterations identified in the resected thyroid lesions were consistent with what has been previously described in the literature. Additionally, we found that in the patients with indeterminate thyroid FNAC with adjunct molecular testing, more than half did not undergo surgical resection. This finding emphasizes the value of adding molecular testing in patients, particularly when attempting to reduce unnecessary surgical intervention.

American Society of Cytopathology Telecytology validation recommendations for rapid on-site evaluation (ROSE).

Telecytology has multiple applications, including rapid onsite evaluation (ROSE) of fine-needle aspiration (FNA) specimens. It can enhance cytopathology practice by increasing productivity, reducing costs, and providing subspecialty expertise in areas with limited access to a cytopathologist. However, there are currently no specific validation guidelines to ensure safe practice and compliance with regulations. This initiative, promoted by the American Society of Cytopathology (ASC), intends to propose recommendations for telecytology implementation. These recommendations propose that the validation process should include testing of all hardware and software, both separately and as a whole; training of all individuals who will participate in telecytology with regular competency evaluations; a structured approach using retrospective slides with defined diagnoses for validation and prospective cases for verification and quality assurance. Telecytology processes must be integrated into the laboratory's quality management system and benchmarks for discrepancy rates between preliminary and final diagnoses should be established and monitored. Special attention should be paid to minimize discrepancies that downgrade malignant cases to benign (false positive on telecytology). Currently, billing and reimbursement codes for telecytology are not yet available. Once, they are, recommendation of the appropriate usage of these codes would be a part of the recommendations. These proposed guidelines are intended to be a resource for laboratories that are considering implementing telecytology. These recommendations can help to ensure the safe and effective use of telecytology and maximize its benefits for patients.

Digital cytology part 1: digital cytology implementation for practice: a concept paper with review and recommendations from the American Society of Cytopathology Digital Cytology Task Force.

Digital cytology and artificial intelligence (AI) are gaining greater adoption in the cytopathology laboratory. However, peer-reviewed real-world data and literature are lacking regarding the current clinical landscape. The American Society of Cytopathology in conjunction with the International Academy of Cytology and the Digital Pathology Association established a special task force comprising 20 members with expertise and/or interest in digital cytology. The aim of the group was to investigate the feasibility of incorporating digital cytology, specifically cytology whole slide scanning and AI applications, into the workflow of the laboratory. In turn, the impact on cytopathologists, cytologists (cytotechnologists), and cytology departments were also assessed. The task force reviewed existing literature on digital cytology, conducted a worldwide survey, and held a virtual roundtable discussion on digital cytology and AI with multiple industry corporate representatives. This white paper, presented in 2 parts, summarizes the current state of digital cytology and AI practice in global cytology practice. Part 1 of the white paper presented herein is a review and offers best practice recommendations for incorporating digital cytology into practice. Part 2 of the white paper provides a comprehensive review of AI in cytology practice along with best practice recommendations and legal considerations. Additionally, the results of a global survey regarding digital cytology are highlighted.

Digital cytology part 2: artificial intelligence in cytology: a concept paper with review and recommendations from the American Society of Cytopathology Digital Cytology Task Force.

Digital cytology and artificial intelligence (AI) are gaining greater adoption in the cytology laboratory. However, peer-reviewed real-world data and literature are lacking in regard to the current clinical landscape. The American Society of Cytopathology in conjunction with the International Academy of Cytology and the Digital Pathology Association established a special task force comprising 20 members with expertise and/or interest in digital cytology. The aim of the group was to investigate the feasibility of incorporating digital cytology, specifically cytology whole slide scanning and AI applications, into the workflow of the laboratory. In turn, the impact on cytopathologists, cytologists (cytotechnologists), and cytology departments were also assessed. The task force reviewed existing literature on digital cytology, conducted a worldwide survey, and held a virtual roundtable discussion on digital cytology and AI with multiple industry corporate representatives. This white paper, presented in 2 parts, summarizes the current state of digital cytology and AI practice in global cytology practice. Part 1 of the white paper is presented as a separate paper which details a review and best practice recommendations for incorporating digital cytology into practice. Part 2 of the white paper presented here provides a comprehensive review of AI in cytology practice along with best practice recommendations and legal considerations. Additionally, the cytology global survey results highlighting current AI practices by various laboratories, as well as current attitudes, are reported.

The current state of digital cytology and artificial intelligence (AI): global survey results from the American Society of Cytopathology Digital Cytology Task Force.

INTRODUCTION: The integration of whole slide imaging (WSI) and artificial intelligence (AI) with digital cytology has been growing gradually. Therefore, there is a need to evaluate the current state of digital cytology. This study aimed to determine the current landscape of digital cytology via a survey conducted as part of the American Society of Cytopathology (ASC) Digital Cytology White Paper Task Force. MATERIALS AND METHODS: A survey with 43 questions pertaining to the current practices and experiences of WSI and AI in both surgical pathology and cytology was created. The survey was sent to members of the ASC, the International Academy of Cytology (IAC), and the Papanicolaou Society of Cytopathology (PSC). Responses were recorded and analyzed. RESULTS: In total, 327 individuals participated in the survey, spanning a diverse array of practice settings, roles, and experiences around the globe. The majority of responses indicated there was routine scanning of surgical pathology slides (n = 134; 61%) with fewer respondents scanning cytology slides (n = 150; 46%). The primary challenge for surgical WSI is the need for faster scanning and cost minimization, whereas image quality is the top issue for cytology WSI. AI tools are not widely utilized, with only 16% of participants using AI for surgical pathology samples and 13% for cytology practice. CONCLUSIONS: Utilization of digital pathology is limited in cytology laboratories as compared to surgical pathology. However, as more laboratories are willing to implement digital cytology in the near future, the establishment of practical clinical guidelines is needed.

Lipomatosis coli, a mimicker of familial polyposis.

Multiple intestinal lipomas (lipomatous polyposis) are quite rare, and they can be quite challenging to diagnose because this condition may be clinically confused with familial adenomatous polyposis with a suggestive family history. Herein, we present a case of lipomatous polyposis that was presented with abdominal pain and, in colonoscopy, had more than 100 polyps. The patient was admitted for surgery with diagnosis of familial polyposis. Resected colon specimen had multiple polyps ranging from 0.1 to 1.5 cm. Microscopically, the polyps were composed of mature adipose tissue with normal overlying mucosa. There were also increased fat cells in the submucosa of the colon adjacent to the polyps. Lipomatous polyposis rarely occurs and can be confused with familial polyposis. Polypectomy is a simple and cost-effective procedure to help in diagnosis and prevent a major surgery.

A Practical Approach to Squamous Abnormalities on Cervical Cytology: Overview of Interpretive Criteria and Guidance for Altering Thresholds in Response to Quality Assurance Findings.

BACKGROUND: Squamous intraepithelial lesions observed in Papanicolaou (Pap) test gynecologic cytology arise as a result of infection of the cervicovaginal tract by human papillomavirus (HPV). The viral cytopathic effect of HPV manifests as koilocytosis, also known as low-grade squamous intraepithelial lesion (LSIL) in The Bethesda System (TBS). Integration of HPV genetic material into the genome of squamous cells can, in some women, result in progressive accumulation of mutations and abnormalities of growth and maturation leading to high-grade squamous intraepithelial lesion (HSIL) and possibly invasive squamous cell carcinoma. Due to morphologic overlap between reactive processes and these changes related to HPV, TBS includes equivocal categories that may be applied to Pap tests with uncertain morphology: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells cannot exclude HSIL (ASC-H). Quality assurance (QA) measures in gynecologic cytology laboratories aim to maximize the sensitivity for LSIL and HSIL lesions while simultaneously keeping the use of ASC-US at reasonable levels. SUMMARY: TBS provides a comprehensive nomenclature for squamous abnormalities encountered in screening, but subjectivity in interpretation remains. QA practices attempt to identify problematic patterns of misinterpretation for correction. KEY MESSAGE: This review aimed to provide practical recommendations for cytology practitioners seeking to alter their interpretive thresholds for ASC-US, LSIL, and HSIL in response to feedback from QA procedures indicating deviation from desired norms.

One procedure-one report: the Re-Imagine Cytopathology Task Force position paper on small tissue biopsy triage in anatomic pathology.

INTRODUCTION: Endoscopic biopsy procedures increasingly generate multiple tissue samples from multiple sites, and frequently retrieve concurrent cytologic specimens and small core needle biopsies. There is currently lack of consensus in subspecialized practices as to whether cytopathologists or surgical pathologists should review such samples, and whether the pathology findings should be reported together or separately. MATERIALS AND METHODS: In December 2021, the American Society of Cytopathology convened the Re-Imagine Cytopathology Task Force to examine various workflows that would facilitate unified pathology reporting of concurrently obtained biopsies and improve clinical care. RESULTS AND CONCLUSIONS: This position paper summarizes the key points and highlights the advantages, challenges, and resources available to support the implementation of such workflows that result in "one procedure-one report".

Assessing the quality of cytopathology whole slide imaging for education from archived cases.

INTRODUCTION: Many institutions have cytopathology case archives for education. Unfortunately, these slides deteriorate over time and have limited accessibility. Whole slide imaging (WSI) can overcome these limitations. However, suboptimal image quality and scanning effort are barriers. MATERIALS AND METHODS: We selected 123 slides from cytopathology study sets for WSI scanning at 400x magnification without z-stacking. The Ventana DP 200 scanner and Virtuoso software were used. Slides were scanned in 2 rounds: the first round of slides was prepared for scanning with light cleaning, and the second round was performed only on slides that had unacceptable WSI quality after thorough cleaning. Slides were assessed with a 4-tier grading system created by the authors. Time to scan each slide was recorded. RESULTS: Within the first round, 96 of 123 (78%) slides scanned were determined to be of acceptable quality. After the second round of scanning, in total, 118 of 123 (95.9%) slides were determined to be of acceptable quality. The average time needed to scan each slide was 213 seconds. CONCLUSIONS: The majority of slides scanned were of acceptable quality in the first round of scanning. After cleaning and rescanning, nearly every slide investigated was of acceptable quality. The primary objective is to provide other institutions that may be considering a similar project a benchmark so that they know what to expect in terms of slide scan success rate and the amount of time needed to digitize slides for educational archiving. This pilot study demonstrates the feasibility of using WSI for cytology education cases.

Cyto-histo correlations of plasmacytoid and micropapillary variants of high-grade urothelial carcinoma: do they fit well in The Paris System for reporting urinary cytology?

INTRODUCTION: Plasmacytoid and micropapillary variants of high-grade urothelial carcinoma (HGUC) exhibit unique histologic morphology and very aggressive clinical behavior. However, the morphology of these 2 variants in urinary cytology is not well studied and evaluated using The Paris System for reporting urinary cytology. MATERIALS AND METHODS: A database search was performed in all patients with the diagnosis of plasmacytoid or micropapillary HGUC. A total of 5 patients with positive urinary cytology cases were identified. The cytomorphology of every urinary cytology case was correlated with the histologic features in the surgical specimens from the same patient. RESULTS: One urine and 4 bladder washings were evaluated. Cytologically, plasmacytoid HGUCs are characterized by single, large tumor cells with hyperchromasia, irregular nuclear membranes, and vacuolated cytoplasm. The nuclear-to-cytoplasmic (N:C) ratio was less than 0.5 in many of the malignant cells due to the abundant cytoplasm. The cytology features of micropapillary HGUC include the presence of micropapillae of tumor cells with no fibrovascular core. Individual high-grade urothelial cells were also identified in all 4 cases, but 1 (25%) of these had only rare cells meeting The Paris System criteria for HGUC due to abundant cytoplasm and lack of hyperchromasia in most malignant cells. CONCLUSIONS: Plasmacytoid and micropapillary variants of HGUC have unique cytomorphologic features in urinary cytology specimens, which are reflective of the corresponding histological findings. These 2 clinically aggressive variants of HGUC may not be as readily interpreted as malignant using The Paris System for reporting urinary cytology, creating potential diagnostic pitfalls.

Rescreening of high-risk HPV positive Papanicolaou tests initially screened as negative is a low yield procedure in the era of HPV genotyping.

INTRODUCTION: Many laboratories rescreen Papanicolaou test slides initially interpreted as negative, but positive for human papillomavirus (HPV) high-risk types, as a quality control measure. We have evaluated the utility of this practice in the era of HPV genotyping as a laboratory improvement project. MATERIAL AND METHODS: Between August 2016 and October 2019, we identified 3618 rescreened Papanicolaou tests with follow-up biopsies. The biopsy results were put into 3 groups: 1) Negative; 2) LSIL: HPV changes or low-grade squamous intraepithelial lesion; and 3) HSIL: high-grade squamous intraepithelial lesion or carcinoma. HPV molecular testing results with subtyping for types 16 and 18 were available for 3117 of these cases. RESULTS: A total of 530 of 2812 Papanicolaou tests (18.8%) with positive HPV results were reinterpreted as cytologically abnormal after rescreening; 75 (14.2%) had a biopsy result of HSIL. The subset positive for HPV types 16/18 had 38 of 133 cytology positive cases diagnosed as HSIL on biopsy vs. 107 of 935 cytology negative cases diagnosed as HSIL on biopsy (28.6% vs. 11.4%, P < 0.0001). The subset positive for "other" (non-16/18) high-risk HPV types had 37 of 397 cytology positive follow-up HSIL vs. 84 of 1288 cytology negative follow-up HSIL (9.3% vs. 6.5%, P = 0.075). CONCLUSIONS: Rescreening has the highest yield in specimens positive for types 16/18. However, for this group colposcopy is recommended regardless of cytology findings, reducing the patient benefit. Routine rescreening of cytology negative/HPV positive Papanicolaou tests has reduced utility when HPV subtyping is performed and should be reconsidered.

Extramedullary multiple myeloma involving the liver and periportal lymph node, diagnosed by EUS-FNA in a patient with cirrhosis.

Extramedullary multiple myeloma (EMM) involving the liver as a focal space-occupying lesion is very rare, especially in the patients with cirrhosis. Here, we report a case of EMM in the liver and periportal lymph node, diagnosed by endoscopic ultrasound guided-fine-needle aspiration (EUS-FNA). A 57-year-old male patient, with history of cirrhosis, presented with abdominal pain and pancytopenia. The abdominal magnetic resonance imaging (MRI) demonstrated a 6.5 cm left hepatic mass with a 1.1 cm malignant-appearing periportal lymph node and diffuse osseous lesions. The cytology specimens from the hepatic mass and the periportal lymph node were obtained through EUS-FNA without rapid on-site evaluation (ROSE). The thin-layer preparations (ThinPrep) showed abundant plasmacytoid cells, which were confirmed to be Kappa-restricted neoplastic plasma cells by the cell block preparations. Later, his serum level of Kappa light chain was found significantly elevated by flow cytometry, which was identified as monoclonal IgA Kappa light chain by serum protein electrophoresis (SPEP) with immunofixation. The patient was diagnosed as IgA multiple myeloma with extramedullary involvement of the liver and periportal lymph node. This is the first case showing the ThinPrep cytomorphologic features of EMM in the liver and periportal lymph node. This case highlights the importance of distinguishing plasma cells from being hepatocytes and lymphocytes on the ThinPrep and also emphasizes the utility of the cell block in the diagnosis of plasma cell neoplasm.

Small core needle biopsies in cytology practice: a survey of members of the American Society of Cytopathology.

INTRODUCTION: The introduction of a new generation of core needle biopsies (CNBs) for endoscopic procedures has prompted reconsideration of the role of cytopathologists in the handling of small biopsies. The American Society of Cytopathology (ASC) has therefore conducted a survey with the intention of elucidating current practices regarding the handling of small CNBs. MATERIALS AND METHODS: The membership of the ASC was invited by email to participate in an online survey over a 2-month period. The survey consisted of 20 multiple choice questions with 2-8 possible responses per question. RESULTS: Of 2651 members contacted by e-mail, 282 (10.6%) responded to the survey questions, including 196 pathologists (69.5%) and 86 cytotechnologists (30.5%). Of these, 265 respondents were from the US/Canada (94.0%), with 156 from academic institutions (58.9%) and 109 from non-academic practices (41.1%); 17 were from other countries (6.0%). In 18.8% of all practices, cytopathologists sign out >90% of small CNBs from endoscopic and radiologically guided procedures; in 36.5% of practices >90% are signed out by surgical pathologists; the remainder have such cases divided more evenly between cytopathologists and surgical pathologists. Responses show that 78.0% of all respondents are interested in signing out more small biopsies in the future, and 80.5% desire increased small biopsy-related resources from the ASC. CONCLUSIONS: The survey responses indicate that practices currently vary widely across institutions. Most indicated an interest in greater incorporation of small biopsies into the practice of cytopathology.

Routine review of ascites fluid from patients with cirrhosis or hepatocellular carcinoma is a low-yield procedure: an observational study.

BACKGROUND: Patients with cirrhosis develop ascites for physiologic reasons that are unrelated to malignant progression. However, physicians performing paracentesis in these patients, often send fluid to the cytology laboratory, sometimes specifically looking for hepatocellular carcinoma (HCC). We have investigated the diagnostic yield of these specimens. MATERIALS AND METHODS: A computerized pathology database search for all ascites fluid cases submitted to the cytology laboratory at a major liver transplant center between November 2004 and April 2008 was performed. Clinical history was obtained for each case. Patients with cirrhosis, with or without HCC, were included in the study. Cytologic diagnoses were compiled and follow-up information was obtained for cases with non-negative findings. RESULTS: A total of 167 specimens from 133 patients ranging from 29 to 85 years of age (mean 56 years) were submitted over the said time period. The causes of cirrhosis included: alcohol - 44; Hepatitis C - 30; Hepatitis B - 6; non-alcoholic steatohepatitis - 7; cryptogenic - 18; other single causes - 6; and multifactorial (alcohol and hepatitis viruses) - 22. Hepatocellular carcinoma (HCC) was present or strongly suspected in 17 patients and had been previously resected in two others. The status of fifteen patients was post liver transplant, with recurrent liver failure. Human immunodeficiency virus was present in seven patients and eight patients had a history of non hepatic malignancies. Among the specimens, 162 were negative, two had atypical lymphocytes worked up for lymphoma, and three had atypical epithelioid cells; none was positive for HCC. Immunohistochemistry demonstrated a mesothelial origin for the atypical epithelioid cells in two cases; in the third case, the patient died shortly after the specimen was collected, with no radiological evidence of HCC. CONCLUSION: Ascites fluid cytology specimens in patients with cirrhosis, even those known or suspected to have HCC, are almost always negative. Atypical cells seen in such specimens should be treated with skepticism since the likelihood that they represent peritoneal spread of HCC is low..

Automated screening of Papanicolaou tests: A review of the literature.

Automated Papanicolaou test screening systems have now been available for over 25 years. Currently two automated screening systems are in widespread clinical use. These are the ThinPrep Imaging System and the FocalPoint GS Imaging System. In their current configurations, both facilitate faster screening by showing a limited number of fields of view (FOV) to cytotechnologists. The FOV are based on the use of proprietary algorithms applied to computerized images of the slide that determine the cells and cell groups with the highest likelihood of abnormality. If all of the FOV are deemed to be negative, the case can be signed out with no additional review; if one or more fields appear possibly abnormal, the entire slide must be manually screened. The United States Food and Drug Administration has ruled that for workload calculation purposes, looking at only the FOV review counts as one-half slide, potentially greatly increasing the number of slides that can be screened. However, follow-up studies of this technology have shown that screening accuracy declines when very large numbers of cases are reviewed per day. Recommendations designed to limit screening volumes to levels that do not jeopardize patient care have therefore been created. The development of fully automated screening that does not rely on human judgment remains an unrealized aspiration. This review covers the history of the development and clinical implementation of automated screening technology with descriptions of the various automated screening systems and their performance as reported in published literature.

A review of the FDA-approved molecular testing platforms for human papillomavirus.

The advent of US Food and Drug Administration (FDA)-approved molecular testing for human papillomavirus (HPV) has resulted in a dramatic shift from cytological testing alone to a combination of cytology and molecular testing for primary HPV screening. HPV testing has quickly become an essential component of daily practice in most laboratories and clinical practices. Although the principle of HPV testing is now familiar, it is important to understand the mechanisms behind these platforms in order to properly interpret the results and understand the limits of each method. HPV tests are more automated and reproducible than cytology, but are by no means perfect. None of these platforms will identify every HSIL/CIN2+ or cancer. This fact must be kept in mind when correlating the results of HPV testing with cytology or biopsy findings. The goal of this paper is to review the FDA- approved molecular testing platforms for HPV, including methodology, limitations, and specifications. The concordance between the platforms will also be discussed. Package inserts of the 5 FDA- approved molecular testing platforms for HPV, as well as a literature review of the platforms, were reviewed and assimilated into the article. Due to the multiple modalities available for detection of hrHPV, the concordance between these assays becomes important. Prior publications have compared HC2, Cervista, cobas, and Aptima, with most studies comparing to HC2 because it is considered the reference standard. With the newly approved BD platform, concordance studies were reviewed as well.

In Vivo and Ex Vivo Microscopy: A Business Plan to Justify the Introduction of Similar Emerging Technologies Into Pathology Practice.

CONTEXT.­: Our patients are now demanding value for their medical diagnoses and treatment in terms of optimal costs, quality, and outcomes. The financial justification for the introduction of new emerging technologies that may better meet these needs will depend on many factors, even if there is an established reimbursement code. In vivo and ex vivo microscopic technologies (IVM and EVM, respectively) will be used as examples of potentially transforming technologies. OBJECTIVE.­: To describe the components of a business plan that ensures all of the ramifications of introducing a new technology into pathology practice have been considered. As well as the financial justification, such a plan should include strategic vision and congruence, the advantages and drawbacks of introducing such technology, and how plans for marketing, implementation, and verification can be operationalized. DATA SOURCES.­: Unlike many pathologists, administrative directors in clinical laboratories already know the components of a financially sound business plan. In addition to the financial justifications, other considerations of such a plan include expense reductions, multiyear buildups in revenue generation, the replacement of other technologies, improved productivity and workflows, additional space, new capital, retrained personnel, and the impact on other departments. CONCLUSIONS.­: Pathologists will learn a business plan format to improve their confidence in making the sound financial justifications needed to consider the introduction of an emerging technology into pathology practice, even when there is initially no obvious revenue stream because formal reimbursement codes have not been established.